There are many life forms, for example, insects, microorganisms, amphibians and human beings which may produce anti-bacterial peptide materials that protect their communities. These anti-bacterial peptides can penetrate lipids on the cell membranes and make them inactive, can also affect protozoon species, germ cells and even viruses, hence such peptides are referred to as super-antibiotics. Anti-bacterial peptides all carry various amounts of positive charge, and their anti-bacterial mechanism lies in the combination of the positive charges carried by the peptides with the negative charges carried by the phospholipids which exist in the bacteria cell wall, creating an ion path on the cell membrane, enhancing the penetrability, causing the bacteria to dissolve and die. Hence the anti-microbial activities of these peptides do not depend on the binding with any specific receptors.
The anti-bacterial peptides exhibit a broad spectrum of antimicrobial activity upon gram-positive and gram-negative bacteria, as well as aerobic and anaerobic bacteria. They are different from antibiotics in that anti-bacterial peptides do not produce drug-resistance effects, even bacteria that have resistance to many types of antibiotics could be suppressed by the anti-bacterial peptides. Further, such anti-bacterial peptides also have inhibitive effect to protozoon species and viruses. As the metabolism products of the anti-bacterial peptides are amino acids, these peptides are of low toxicity for host cells. In summary, the anti-microbial peptides are a class of compounds with wide prospects of being used for anti-microbial drugs.
Magainins are a category of naturally occurring anti-bacterial peptides derived from frog skin with anti-bacterial effects. Magainins has been extensively studied up till now, they have such features as being easy to be synthesized, low in cost and little possibility of hemolysis.
U.S. Pat. No. 5,589,364 disclosed a method by which the Magainin II peptide having 23 amino acids can be prepared using bioengineering, techniques. Magainin II (hereinafter referred as naturally occurring Magainin, wild-type Magainin or Magainin) is a type of the naturally occurring frog-skin anti-bacterial peptide, having amino acid sequence shown as below:
[SEQ ID NO.:17]Gly-Ile-Gly-Lys-Phe-Leu-His-Ser-Ala-Lys-Lys-Phe-Gly-Lys-Ala-Phe-Val-Gly-Glu-Ile-Met-Asn-Ser-OH
in which:
Gly stands for glycine, Ile for isoleucine, Lys for lysine, Phe for phenylalanine, Leu for leucine, His for histidine, Ser for serine, Ala for alanine, Val for valine, Glu for glutamic acid, Met for methionine and Asn for asparaginate.
U.S. Pat. No. 6,183,992 disclosed a method to produce MSI-78 (22 amino acids), a derivative of magainin, having the amino acid sequence shown as below:
[SEQ ID NO.:18]Gly-Ile-Gly-Lys-Phe-Leu-Lys-Lys-Ala-Lys-Lys-Phe-Gly-Lys-Ala-Phe-Val-Lys-Ile-Leu-Lys-Lys-NH2
It has been reported in ADIS NEW DRUG PROFILE by Harriet M. Lamb, etc., that the Magainin derivative MS1-78 shows obvious curative effect in treating trauma infection and crura ulceration caused by the diabetes mellitus.